Nicorandil reduces myocardial infarct size by opening the K(ATP) channel in rabbits.
We examined whether nicorandil reduces myocardial infarct size (1) when administered before ischemia, and (2) when administered before reperfusion, and whether (3) infarct size is influenced by the plasma nicorandil concentration and the opening of the K(ATP) channel. Anesthetized open-chest Japanese white male rabbits were subjected to a 30 min coronary occlusion (ischemia) and a 48 h reperfusion in the following six groups; Group 1 (n=9): control group, Group 2 (n=9): pre-ischemia to post-reperfusion group (nicorandil 10 microg/kg/min, i.v.), Group 3 (n=7): pre-ischemia to post-reperfusion+glibenclamide group (glibenclamide 0.3 microg/kg, i.v.+nicorandil 10 microg/kg/min, i.v.), Group 4 (n=8): pre-reperfusion to post-reperfusion group (nicorandil 10 microg/kg/min, i.v.), Group 5 (n=8): pre-ischemia low-dose group (nicorandil 10 microg/kg/min for 5 min i.v.), Group 6 (n=7): pre-ischemia high-dose group (nicorandil 100 microg/kg/min for 5 min i.v.). The plasma nicorandil concentrations were measured from blood samples taken immediately before the ischemia. After the 48 h reperfusion, the size of the infarct was measured histologically with immunohistochemical actin staining and expressed as a percentage of the area at risk.


RESULTS
Infarct sizes were as follows; Group 1 (control): 41.0+/-3.5%, Group 2: 31.3+/-2.0% (P<0.05 vs. control), Group 3: 40.9+/-3.4%, Group 4: 45.2+/-4.4%, Group 5: 35.8+/-3.3%, Group 6: 25.2+/-3.9% (P<0.05 vs. control). Infarct size was inversely correlated with the plasma nicorandil concentrations (y=-0.031x+41.0, r=0.65, P<0.05).


CONCLUSIONS
The pre-ischemic but not post-ischemic administration of nicorandil reduced the size of myocardial infarct by opening the K(ATP) channels, and this effect was dependent on the plasma nicorandil concentrations immediately before the ischemia induced in rabbits.
Ohno
Y
Y
Second Department of Internal Medicine, Gifu University School of Medicine, Japan.
Minatoguchi
S
S
Uno
Y
Y
Kariya
T
T
Arai
M
M
Yamashita
K
K
Fujiwara
T
T
Fujiwara
H
H
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D016014:Linear Models; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D020108:Nicorandil; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000819:agonists / Q000187:drug effects*; D011817:Rabbits; D013997:Time Factors; D014665:Vasodilator Agents / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D014693:Ventricular Fibrillation
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil; D005905:Glyburide